Abdominal Adhesions In Rats Research Articles

Treatment with a probiotic combination reduces abdominal adhesion in rats by decreasing intestinal inflammation and restoring microbial composition.

Abdominal adhesions refer to abnormal adhesions which cause a series of complications in numerous patients. In the present study, the beneficial effect of a combination of probiotics (Lactobacillus plantarum, L. acidophilus, L.rhamnosus and Bifidobacterium animalis) on abdominal adhesions in a rat model were verified. The present results indicated that probiotic treatment significantly reduced the levels of proinflammatory factors interleukin (IL)‑1β, IL‑6 and TNF‑α in serum and intestinal tissue (P<0.05), and markedly downregulated the inflammatory (TLR4/NF‑κB) and fibrotic (TGF‑β1/Smad) signalling pathways in intestinal tissue, especially in the prevention group (P<0.01). The high‑throughput sequencing results further supported that the probiotics significantly increased the relative abundance of probiotic Bacteroidetes (at the phylum level), Bacteroidales (at the order level), Lactobacillales (at the order level) and Lactobacillus (at the genus level), and markedly reduced the number of pathogenic Proteobacteria (at the phylum level), Erysipelotrichales (at the order level), Verrucomicrobiales (at the order level), Klebsiella (at the genus level) and Serratia (at the genus level). In conclusion, probiotics can effectively reduce abdominal adhesions by restoring the microbial balance and reducing inflammation and fibrosis caused by surgery.

Effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway

Objective To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway. Methods Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 220-250 g, were divided into 4 groups (n = 10 each) using a random number table method: sham operation group (Sham group), abdominal adhesion group (AA group), dexmedetomidine group (DEX group) and dexmedetomidine plus methyllycaconitine group (DEX-M group). The rat model of abdominal adhesions was established by cecal friction method.In Sham group, abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups, normal saline 2 ml and α7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4 μg/g (dissolved in 2 ml normal saline) were injected, respectively, and dexmedetomidine 10 μg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion, Phillips method was used for scoring, and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1 (TGF-β1) concentrations in ascites and tumor necrosis factor-alpha (TNF-α) concentrations in serum.The rats were then sacrificed, and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope. Results Compared with group Sham, the abdominal adhesion score and serum TNF-α concentrations were significantly increased in AA and DEX-M groups, and the TGF-β1 concentration in ascites was significantly increased in AA, DEX and DEX-M groups (P 0.05), and the pathological changes of caecum tissue, contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX. Conclusion Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions, and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats. Key words: Dexmedetomidine; Injections, intraperitoneal; Tissue adhesions; Cholinergic anti-inflammatory

Ligustrazine nanoparticles nano spray's activation on Nrf2/ARE pathway in oxidative stress injury in rats with postoperative abdominal adhesion.

Postoperative abdominal adhesions formation is considered a significant clinical entity implicating the healing process following major pelvic and abdominal surgery, with serious clinical complications and need for substantial health care expenditures. However, setting a physical barrier between the damage site and the neighboring tissues is a convenient and highly valid way to minimize or prevent peritoneal adhesions. The present experimental study evaluated the preventive effect of ligustrazine nanoparticles nano spray (LNNS) on postoperative abdominal adhesion in rats and explored its mechanism. Sixty male Sprague Dawley (SD) rats were randomly divided into sham operation group, control group, sodium hyaluronate group and low, medium, and high dose LNNS groups. All groups were prepared with abdominal adhesion models except for the sham operation group. The models were made by opening the abdominal cavity to and filing the serosa in ileocecal junction. The abdominal cavity of rats in the sham operation group were only opened and sutured. The wound surface of rats in the sodium hyaluronate group, low, medium, and high dose LNNS groups were sprayed with sodium hyaluronate gel (0.5 mL/kg) and LNNS (2.5, 5, and 10 mL/kg). Rats in each group were sacrificed 7 days later. Degree of adhesion was evaluated by naked eyes and the pathological sections were scored afterwards. The collagen synthesis in adhesion tissues was detected by Masson's trichrome stain, and the activities of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in peritoneal fluid were detected with the method of chromogenic substrate. Levels of TNF-α and IL-1β in serum, and the protein levels of MCP-1 and MMP-9 in adhesion tissues were detected by ELISA and. immunohistochemistry respectively. RT-PCR and Western blot were utilized to identify the expression levels of Nrf2, heme-oxygenase-1, NQO1 mRNA and protein in adherent intestinal tissues. Compared with the control group, the incidence of postoperative abdominal adhesions decreased in the low, medium and high dose LNNS groups, while the expression of SOD in the peritoneal fluid significantly increased. The expression levels of ROS, MDA and NO were reduced remarkably (P<0.05), so were the expression levels of serum TNF-α and IL-1β (P<0.01) and the expression of MCP-1 protein in adhesion tissues. The MMP-9 protein expression, and Nrf2, heme-oxygenase-1, NQO1 mRNA and protein expressions increased. LNNS with medium or high dose can significantly reduce the incidence of postoperative abdominal adhesions, the mechanism of which may be the activation of Nrf2/ARE pathway, resulting in the up-regulation of Nrf2, heme-oxygenase-1, NQO1 and mRNA expression, as well as the levels of TNF-α and IL-1β in peripheral blood and the expression of MCP-1 protein in adhesion tissues. Meanwhile, the content of MMP-9 protein in adhesion tissues were raised, and oxidative stress and inflammatory response are released.

Usefulness of chymase inhibitor for prevention of abdominal adhesion in rats

Usefulness of chymase inhibitor for prevention of abdominal adhesion in rats

Evaluation of breviscapine on prevention of experimentally induced abdominal adhesions in rats

BackgroundAdhesion formation, which results from mechanical peritoneal damage, tissue ischemia, or the presence of foreign materials, is a complicated process. The formation of adhesions is associated with inflammatory response and extracellular matrix deposition in response to injury. Although the pathophysiology of adhesion formation is widely understood, an absolute solution to this problem does not exist yet. As a main component of Erigeron breviscapus, breviscapine has exhibited the ability of anti-inflammatory and antifibrosis on many diseases. The purpose of this study was to investigate the effect of breviscapine on the development of postoperative intra-abdominal adhesions in Wistar rats. MethodsAbdominal adhesions were induced by scraping the cecum in rats. Various dosages of breviscapine drugs were administered for 10 days after surgery. On the 11th day after surgery, the levels of interleukin (IL) 18, IL-6, tumor necrosis factor α in blood serum and transforming growth factor β1 (TGF-β1), connective tissue growth factor, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) in peritoneal fluid were determined by enzyme linked immunosorbent assay. The expression of Smad7 and TGF-β1 in rat cecum tissue was evaluated by Western blot analysis. Grades of intestinal adhesion were ranked by macroscopic observation. ResultsThe intraperitoneal administration of breviscapine is effective on the prevention of the formation of postoperative adhesions in rats. Breviscapine decreased the levels of IL-18, IL-6, and tumor necrosis factor-α in blood serum and TGF-β1, connective tissue growth factor, PAI-1 in peritoneal fluid. But the levels of tPA and the ratio of tPA and PAI-1 in peritoneal fluid were increased. In addition, breviscapine significantly inhibited the expression of TGF-β1 and increased the level of Smad7 in the rat cecum tissue. ConclusionsThese results suggested that intraperitoneal administration of breviscapine was effective in preventing intra-abdominal adhesion formation in rats. Breviscapine appears to have synergetic effects which could decrease fibrosis by inhibiting inflammation, upregulating peritoneal fibrinolytic activity and regulating the TGF and/or Smad signaling pathway. These data indicated a potential new therapeutic use of breviscapine on adhesion prevention.

Evaluation of ligustrazine on the prevention of experimentally induced abdominal adhesions in rats

ObjectiveTo determine the effects of ligustrazine on the prevention of postoperative intra-abdominal adhesions in rats. Materials and methodsAbdominal adhesions were induced by scraping the cecum of rats. Various dosages of ligustrazine were administered for 10 days after surgery. Grades of abdominal adhesions were ranked by macroscopic observation on the 11th day after surgery. Meanwhile, the levels of IL-1β, IL-6, TNF-a in blood serum and TGF-β1, CTGF in peritoneal fluid were determined by ELISA assay. In the cell experiment, the secretion of FN and CTGF undergoing stimulation with TGF β1 in the culture fluid of rat peritoneal mesothelial cells (RPMC) were measured by ELISA assay. And the expression of Smad7 and p-smad 2/3 in RPMC were evaluated by western blot analysis. ResultsLigustrazine remarkably alleviated the adhesions at the dose of 30 mg/kg and 60 mg/kg compared with the non-treated surgery group (p < 0.05). Ligustrazine decreased the levels of IL-1β, IL-6, TNF-α in blood serum and the expression of TGF-β1, CTGF in the peritoneal fluid in dose-dependent manner. In the cell experiment, ligustrazine markedly attenuated TGF-β1 induced upregulation of FN and CTGF in RPMC. Meanwhile, ligustrazine significantly inhibited the expression of pSmad 2/3 and increased the level of Smad7 in the RPMC. ConclusionsLigustrazine is a potent postoperative adhesion preventer by inhibiting inflammation and regulating the TGF/Smad signaling pathway.

Biodegradable and Thermosensitive Monomethoxy Poly(ethylene glycol)–Poly(lactic acid) Hydrogel as a Barrier for Prevention of Post-Operative Abdominal Adhesion

Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.

Nuclear expression of μ‐opioid receptors in a human mesothelial cell line

1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation of experimentally induced postoperative abdominal adhesions in rats. Mesothelial cells may participate in adhesion formation by secreting mediators that interfere negatively with fibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesion mediators from mesothelial cells. This study aimed to investigate whether human mesothelial cells express MOR-1; if so, such could constitute a site of action for morphine in adhesion prevention. 2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared for immunocytochemistry and Western blotting. 3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in the nuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to those obtained with a control lysate from cells known to express MORs. In addition, we found MOR-1 expression with nuclear and cytoplasmatic localization in biopsies from human abdominal adhesions. 4 The current findings may suggest that morphine could interact directly with mesothelial cells via MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering with the release of pro-adhesion factors from these cells.

In vivo performance of antibiotic embedded electrospun PCL membranes for prevention of abdominal adhesions

The aim of this study was to prepare nonwoven materials from poly(epsilon-caprolactone) (PCL) and their antibiotic containing forms by electrospinning, so as to prevent postsurgery induced abdominal adhesions in rats. epsilon-Caprolactone was first polymerized by ring-opening polymerization, and then it was processed into matrices composed of nanofibers by electrospinning. A model antibiotic (Biteral) was embedded within a group of PCL membranes. In the rat model, defects on the abdominal walls in the peritoneum were made to induce adhesion. The plain or antibiotic embedded PCL membranes were implanted on the right side of the abdominal wall. No membrane implantation was made on the left side of the abdominal wall that served as control. Macroscopical and histological evaluations showed that using these barriers reduces the extent, type, and tenacity of adhesion. The antibiotic embedded membranes significantly eliminated postsurgery abdominal adhesions, and also improved healing.

Halofuginone--an inhibitor of collagen type I synthesis--prevents postoperative formation of abdominal adhesions.

To evaluate the effects of halofuginone, a specific inhibitor of collagen type I synthesis, on the postoperative formation of abdominal adhesions in rats. Postoperative adhesions remain the leading cause of small bowel obstruction in the Western world. Surgical trauma causes the release of a serosanguineous exudate that forms a fibrinous bridge between two organs. This becomes ingrown with fibroblasts, and subsequent collagen deposition leads to the formation of a permanent adhesion. Most of the drugs used have been clinically ineffective, and none has been specific to a particular extracellular matrix molecule. Therefore, there are serious concerns about the toxic consequences of interfering with the biosynthesis of other collagens, other matrix proteins, or vital collagen-like molecules. Adhesions were induced by scraping the cecum until capillary bleeding occurred. The adhesions were scored 21 days later. Halofuginone was either injected intraperitoneally (1 microg/25 g body weight) every day, starting on the day of operation, or added orally at concentrations of 5 or 10 mg/kg, starting 4 days before the operation. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, total collagen was estimated by Sirius red staining, and collagen type III was detected by immunohistochemistry. The adhesions formed between the intestinal walls were composed of collagen and were populated with cells expressing the collagen alpha1(I) gene. Regardless of the administration procedure, halofuginone significantly reduced the number and severity of the adhesions. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the operated rats, thus reducing collagen content to the control level. In fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent inhibition of collagen alpha1(I) gene expression and collagen synthesis. Collagen type III levels were not altered by adhesion induction or by halofuginone treatment. Upregulation of collagen synthesis appears to have a critical role in the pathophysiology of postoperative adhesions. Halofuginone, an inhibitor of collagen type I synthesis, could be used as an important tool in understanding the role of collagen in adhesion formation, and it may become a novel and promising antifibrotic agent for preventing postoperative adhesion formation.

Formation of Abdominal Adhesions Is Inhibited by Antibodies to Transforming Growth Factor-β1

Transforming growth factor-β (TGF-β) is an important factor in regulating the inflammatory response and the production of extracellular matrix by fibroblasts. These two processes are linked in the formation of fibrous adhesions after abdominal surgery. When the mesothelium is injured a fibrin strand is produced which is populated first by inflammatory cells then by fibroblasts which secrete extracellular matrix forming a permanent adhesion. TGF-β promotes both chemotaxis of monocytes and the production of extracellular matrix by fibroblasts. We have used a model of abdominal adhesions in rats in which a circle of peritoneum is dissected and then sutured into place again. After 2 weeks the rats are euthanized and the adhesions are scored. Six groups of 10 rats each underwent this surgery. Group I served as the operative control. Group II was treated with saline which was injected immediately after surgery and on Days 1 and 2 after surgery (vehicle control). Using the same protocol with saline as vehicle, the other four groups of rats were treated with nonspecific IgG (150 μg per day), anti-TGF-β (panspecific, 167 μg per day), anti-TGF-β1 (67 μg per day), or anti-TGF-β2 (50 μg per day). The rats injected with anti-TGF-β1 had significantly lower adhesion scores (P< 0.05) than the controls. Rats injected with anti-TGF-β2 or anti-TGF-β (panspecific) did not differ significantly from the control saline-injected rats. The results indicate that specifically reducing levels of TGF-β1 alone can be effective in preventing abdominal adhesions.

Urokinase does not prevent abdominal adhesion formation in rats.

Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation.

Cianidanol ( [+]-cyanidanol-3) prevents the development of abdominal adhesions in rats.

Abdominal adhesions were experimentally induced in rats by gentle scraping. Severe adhesions developed in 38.7% of the control animals. The flavonoid cianidanol ( [+]-cyanidanol-3), an in vitro inhibitor of procollagen production, was administered intragastrically or intraperitoneally in doses of 9 to 72 mg per rat. Administered intraperitoneally at a dose of 36 or 72 mg per rat, cianidanol substantially inhibited adhesion formulation, when given immediately, three days, or five days after surgery. Oral administration of the drug was less effective in preventing the formation of adhesions. Thimerosal, another connective-tissue inhibitor, was found to be toxic at doses of 2.5 or 5 mg per rat, and its effect on the prevention of adhesion formation was poor. The ability of cianidanol to inhibit the development of abdominal adhesions in rats suggests that a possible approach to treatment is to inhibit the production of procollagen and thus prevent the formation of the collagenous fibers that are the cause of adhesions.